WO2019002678A1 - Puce microfluidique et procédé de production d'une puce microfluidique - Google Patents

Puce microfluidique et procédé de production d'une puce microfluidique Download PDF

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Publication number
WO2019002678A1
WO2019002678A1 PCT/FI2018/050492 FI2018050492W WO2019002678A1 WO 2019002678 A1 WO2019002678 A1 WO 2019002678A1 FI 2018050492 W FI2018050492 W FI 2018050492W WO 2019002678 A1 WO2019002678 A1 WO 2019002678A1
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WO
WIPO (PCT)
Prior art keywords
channel
microfluidic chip
sample
inner flow
volume
Prior art date
Application number
PCT/FI2018/050492
Other languages
English (en)
Inventor
Tiina Maaninen
Annukka KOKKONEN
Marika Kurkinen
Sanna Aikio
Original Assignee
Teknologian Tutkimuskeskus Vtt Oy
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Teknologian Tutkimuskeskus Vtt Oy filed Critical Teknologian Tutkimuskeskus Vtt Oy
Priority to US16/627,373 priority Critical patent/US11759782B2/en
Priority to EP18823238.3A priority patent/EP3645165A4/fr
Priority to CN201880044196.0A priority patent/CN110891686B/zh
Publication of WO2019002678A1 publication Critical patent/WO2019002678A1/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502723—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by venting arrangements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502707—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the manufacture of the container or its components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/502746—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means for controlling flow resistance, e.g. flow controllers, baffles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • B81B1/002—Holes characterised by their shape, in either longitudinal or sectional plane
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • B81B1/002—Holes characterised by their shape, in either longitudinal or sectional plane
    • B81B1/004—Through-holes, i.e. extending from one face to the other face of the wafer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
    • B81B1/006—Microdevices formed as a single homogeneous piece, i.e. wherein the mechanical function is obtained by the use of the device, e.g. cutters
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C1/00—Manufacture or treatment of devices or systems in or on a substrate
    • B81C1/00015—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems
    • B81C1/00023—Manufacture or treatment of devices or systems in or on a substrate for manufacturing microsystems without movable or flexible elements
    • B81C1/00119—Arrangement of basic structures like cavities or channels, e.g. suitable for microfluidic systems
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N35/1009—Characterised by arrangements for controlling the aspiration or dispense of liquids
    • G01N35/1016—Control of the volume dispensed or introduced
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0605—Metering of fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/12—Specific details about manufacturing devices
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/069—Absorbents; Gels to retain a fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
    • B01L2300/0864—Configuration of multiple channels and/or chambers in a single devices comprising only one inlet and multiple receiving wells, e.g. for separation, splitting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/12—Specific details about materials
    • B01L2300/123—Flexible; Elastomeric
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/16—Surface properties and coatings
    • B01L2300/161—Control and use of surface tension forces, e.g. hydrophobic, hydrophilic
    • B01L2300/165—Specific details about hydrophobic, oleophobic surfaces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0406—Moving fluids with specific forces or mechanical means specific forces capillary forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2201/00—Specific applications of microelectromechanical systems
    • B81B2201/05—Microfluidics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
    • B81B2203/00—Basic microelectromechanical structures
    • B81B2203/03—Static structures
    • B81B2203/0323—Grooves
    • B81B2203/0338—Channels
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2201/00—Manufacture or treatment of microstructural devices or systems
    • B81C2201/01—Manufacture or treatment of microstructural devices or systems in or on a substrate
    • B81C2201/0101—Shaping material; Structuring the bulk substrate or layers on the substrate; Film patterning
    • B81C2201/0147—Film patterning
    • B81C2201/015—Imprinting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B81—MICROSTRUCTURAL TECHNOLOGY
    • B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
    • B81C2203/00—Forming microstructural systems
    • B81C2203/03—Bonding two components

Definitions

  • the present disclosure relates to devices for optical analysis.
  • the disclosure relates to devices for receiving a liquid sample for optical analysis. More specifically, the disclosure relates to a microfluidic chip and a method for the manufacture of a microfluidic chip.
  • Microfluidic chips are widely used to facilitate a host of different analysis methods performed on liquid samples. While there are very sophisticated devices designed for laboratory environment, there is a growing need for basic analysis devices for patients to use themselves outside a treatment facility. To avoid the need to administer a specific amount of sample fluid into the analysis device with a precision tool, such as a pipette, the most preferred devices designed for domestic use are equipped with a metered sample volume to allow for overflow of the sample liquid without jeopardizing the analysis.
  • EP 2875866 Al discloses a fluidic device including an overspill chamber for collecting the excess sample.
  • a novel microfluidic chip is therefore proposed for performing a chemical or biochemical test in a metered reaction volume.
  • the microfluidic chip has a body which defines an inner flow volume.
  • An inlet has been provided to the body for connecting the inner flow volume to the ambient space.
  • a waste channel forms part of the inner flow volume and is in fluid communication with the inlet.
  • a sample channel also forms part of the inner flow volume and is in fluid communication with the inlet.
  • the sample channel includes a first hydrophobic stop and a second hydrophobic stop at a distance from the first hydrophobic stop so as to provide a metered reaction volume there between.
  • An expelling channel is in fluid communication with the metered reaction volume of the sample channel through the first hydrophobic stop.
  • a sample reservoir is in fluid communication with the metered reaction volume of the sample channel through the second hydrophobic stop.
  • a method is also proposed for the manufacture of such a micro fluidic chip.
  • at least two substrates are provided, wherein the substrates are flexible enough to enable continuous roll-to-roll, stop-and-go roll, or sheet manufacturing.
  • An inner flow channel is formed to one or more of the at least two substrates.
  • a passage is formed to one or more of the at least two substrates so as to provide an inlet to the inner flow channel.
  • Two hydrophobic stops are provided to the inner flow channel at a distance from one another so as to provide a metered reaction volume there between.
  • a capture antibody is provided to the reaction volume for establishing a reaction zone.
  • the substrates are superposed on each other and laminating together to form the microfluidic chip by roll-to- roll, stop-and-go roll, or sheet manufacturing.
  • the invention is defined by the features of the independent claims. Some specific embodiments are defined in the dependent claims. [0007] Considerable benefits are gained by virtue of the novel proposition. Because the inner flow channel is arranged in a particular way, two-dimensional fluid flow is enough to facilitate the pursued optical analysis. Accordingly, there is no need for magnetic or otherwise complex actuators to meter the desired sample volume for analysis. On the other hand the two-dimensional fluid flow enables advantageous manufacturing techniques to mass produce the device for domestic use. Further benefits gained with particulars of specific embodiments are discussed here after.
  • FIGURE 1 illustrates a schematic top view of a microfluidic chip in accordance with at least some embodiments of the present invention
  • FIGURE 2 illustrates a perspective exploded view of the microfluidic chip of FIGURE 1.
  • a novel micro fluidic chip 100 having an inner flow volume made by a network of channels 20, 30, 40, 51, 52 is constructed into a body 200 with a preferably at least partly transparent top plate to facilitate optical analysis.
  • the components of the inner flow volume are in fluid connection with each other, i.e. the components are connected to each other so as to allow the passage of fluid from one another. That said, liquid flow is restricted to certain parts of the inner flow volume, namely the expelling channel 40 and sample reservoir 51, by means of hydrophobic stops while gas flow remains free.
  • FIGURE 2 illustrates one example of constructing a micro fluidic chip.
  • micro fluidic refers to the microliter scale of the device.
  • the volume of the inner flow volume is in the approximate range of 1 to 510 microliters.
  • the microfluidic chip is formed by a body 200, which has several layers. Firstly there is a bottom substrate 230, which may be formed of a polymer, such as PPP or PMA, glass, metal, preferably elastically deformable metal, paper, preferably coated paper, or any preferably hydrophilic material.
  • the bottom substrate 230 is preferably solid over the sections of the body 200 that contain channels to limit the flow to a two-dimensional domain.
  • An intermediate substrate 220 is placed on top of the bottom substrate 230.
  • the intermediate substrate 220 defines the shape and extent of the inner flow volume of the microfluidic chip. The sections of the inner flow volume are discussed in greater detail here after.
  • the intermediate substrate 220 includes openings extending through the thickness of the intermediate substrate 220 to form the inner flow volume.
  • superposed on the intermediate or bottom substrate is a top substrate 210.
  • the top substrate 210 is preferably transparent for wavelengths used in optical testing. Typical wavelengths used in optical tests range from ultraviolet to infrared range including the visible range. According to a particularly advantageous embodiment, the top substrate 210 is see-through.
  • the top substrate 210 includes an opening for acting as an inlet 10 for introducing fluid into the inner flow volume which is formed into the space between the top and bottom substrates 210, 230 and defined by the intermediate substrate 220.
  • the inner flow volume could be produced to the bottom or top substrate as well by removing material or by casting the block forming the bottom or top substrate (not shown). Also, the inlet could be made to the bottom substrate. [0012]
  • the body 200 may be made of three layers as shown in FIGURE 2. The body
  • the body 200 may alternatively be formed of two layers or more than three layers (not shown).
  • the body 200 may be made flexible to enable continuous roll to roll or stop-and-go roll.
  • sheet manufacturing process may be applied.
  • flexible may be seen as the ability to experience elastic deformation to a bending radius of 300 mm, preferably 200 mm, at 20 degrees Celcius.
  • Such a construction enables manufacturing by means of a continuous or stop-and-go roll or sheet process which may include hot-embossing, diecutting, laser cutting, hybrid assembly, screen printing, gravure printing, flexo printing, inkjet printing, slot die coating, reverse gravure printing, uv-curing, laser ablation, nano-imprinting and lamination. Any combination of such go roll or sheet processes will lead to an effective manufacturing process for mass production.
  • the manufacturing process makes device is made by laminating.
  • the bottom, intermediate and top substrates 230, 220, 210 are prepared in any order or simultaneously.
  • the bottom substrate 230 may be prepared by producing the hydrophobic stops to the bottom substrate 230 with screen printing, die cut or slot die coating, gravure coating, reverse gravure coating, inkjet printing, flexo printing, uv-curing, nano-imprinting, or any suitable method.
  • the intermediate substrate 220 may be prepared by providing suitable channels by die cutting.
  • the sample reservoir 51 and/or the waste reservoir 52 may be produced with a similar method at this stage or later.
  • the intermediate substrate 220 is laminated to the top substrate 210 to create a top sub-assembly 210, 220.
  • the opening forming the inlet 10 is formed to the top substrate 210 and intermediate substrate 220 by laser or die cutting.
  • the capture antibodies needed in the optical analysis performed with the device may be provided at this or an earlier stage.
  • the capture antibodies may be dispensed with a dispenser, inkjet printer, or a similar device.
  • the capture antibodies may be dispensed over the entire sample channel 30 or only to a limited detection zone 33 of the sample channel 30. If absorption material is used, the material is preferably installed at this stage.
  • the bottom substrate 230 is laminated to the top sub-assembly 210, 220.
  • the manufacturing process described above for a three layer construction may be modified for a two layer construction including a bottom and a top substrate without an intermediate layer there between (not shown).
  • the flow channel may be formed to any substrate or substrates in the device by shaping the interface surface of the substrates.
  • the flow channel forming recess may be provided to the top or bottom substrate or both.
  • the flow channel may be produced by removing material by laser cutting or laser ablation or the channel may be molded by hot embossing or nano-imprinting, for example.
  • the hydrophobic stops may be produced as above. Accordingly, the top substrate is laminated directly on top of the bottom substrate, wherein the inner channel is formed there between.
  • the body comprises three layers as shown in FIGURE 2, but instead of forming the flow channel by the cavities in the intermediate layer alone, also the top or bottom substrate or both comprise recessed areas which participate in forming the inner flow volume.
  • FIGURE 1 reveals the shape and functions of the inner flow volume more clearly.
  • the inlet 10 formed to the top substrate 210 connects the inner flow volume of the body 200 to the outside space.
  • the inner flow volume is designed to create a network permitting free air flow within the network.
  • a sample channel 30 encased by the body 200.
  • the sample channel 30 is located at the bottom of the inlet 10.
  • the mass of the liquid in the relatively large inlet 10 urges liquid down the sample channel 30, which movement is further advanced by capillary action. Accordingly, the inlet 10 and sample channel 30 are dimensioned to facilitate such action.
  • the inlet 10 may be equipped with a seal 90
  • the seal 90 may be completely detached and configured to be attached to the body 200 or the seal 90 may be attached to the body 200 so as to be manipulated to seal or open the inlet 10. More specifically the seal 90 may be toggled between an open state, in which the seal 90 permits a flowing passage of fluid into the inner flow volume, and a closed state, in which the seal 90 prevents a flowing passage of fluid into the inner flow volume.
  • a simple example of such a seal 90 would be a piece of adhesive tape which may be unfolded from an open state adjacent to the inlet 10 into a closed state covering the inlet 10. Another simple example would be a cork.
  • the sample channel 30 has a first section 31 extending from the inlet 10 to one direction and a second section 32 extending from the first section to a different direction, particularly to an orthogonal direction.
  • the sample channel 30 exhibits a corner between two sections 31, 32.
  • the sample channel 30 has been provided with two hydrophobic stops 61, 62.
  • a first hydrophobic stop 61 has been positioned at a distance from a second hydrophobic stop 62, whereby a metered reaction volume is created to a section extending between the hydrophobic stops 61, 62.
  • the volume of the metered reaction volume is defined by the distance between the hydrophobic stops 61, 62, the thickness of the intermediate substrate 220 and the breadth of the sample channel 30.
  • the second section 32 of the sample channel 30 forms the metered reaction volume.
  • the stop may be achieved by increasing the topography, i.e. surface roughness, or surface energy of the channel at the appropriate locations.
  • hydrophobic substance such as carbon ink, UV curable acrylate ink, wax, micro structures, nano structures, and the like
  • Another way would be to apply a Teflon or other hydrophobic coating onto the surface of the sample channel 30 over a small section at an appropriate location.
  • Yet another way would be grind the surface of the sample channel 30 with an abrasive material so as to increase the surface roughness and to establish a hydrophobic stop.
  • the hydrophobic stop is able to prevent a sample fluid at atmospheric pressure from flowing past the first and second hydrophobic stops 61, 62 by capillary action alone.
  • difference in surface energy of the inner flow channel at the hydrophobic stop 61, 62 and the rest of the inner flow channel is 10 mN/m or more, more preferably 20 mN/m or more.
  • the detection zone 33 is a portion of the inner flow channel to which the analytes are collected and where the measurement signal is detected.
  • the detection zone 33 may take any shape, such as a quadrilateral shape shown in FIGURE 1, and may be for example a couple of millimetres per side to avoid the need for microscopic magnification.
  • the detection zone 33 comprises a capture antibody or several capture antibodies dispensed on flow surface the sample channel 30.
  • the sample channel 30, preferably the second portion 32 thereof - i.e. the reaction volume - may be provided with a fluorescence substance to enable competitive or non-competitive immunoassay.
  • a sample reservoir 51 Connected to the sample channel 30, particularly to the second section 32, more particularly to the second end of the second section 32 of the sample channel 30, is a sample reservoir 51.
  • the sample reservoir 51 may be encased by the body 200 as shown in the FIGURES or it may be arranged outside the body as an external reservoir (not shown).
  • the sample reservoir 51 is connected to the sample channel 30 through the second hydrophobic stop 62.
  • the sample reservoir 51 is set to receive liquid expelled from the sample channel 30. Accordingly, the sample reservoir 51 is dimensioned to receive and hold the volume of liquid held by the sample channel 30. In other words, the volume of the sample reservoir 51 is equal to or larger than that of the sample channel 30.
  • the sample reservoir 51 may contain an absorbent material, such as paper, fabric, silica, etc., or a capillary pump to further attract the liquid.
  • the sample reservoir 51 is in fluidic connection to the ambient space through an air outlet 11 for exhausting air trapped in the inner flow volume, when liquid is being pushed along the channel 30.
  • the air outlet 11 may be a simple hole or a valved passage provided to the top substrate 210 or bottom substrate 230 or both.
  • an expelling channel 40 Connected to the sample channel 30, particularly to the second section 32, more particularly to the first end of the second section 32 of the sample channel 30, is an expelling channel 40.
  • the expelling channel 40 is encased by the body 200.
  • the expelling channel 40 is connected to the sample channel 30 through the first hydrophobic stop 61.
  • the purpose of the expelling channel 40 is to act as a port for pressurizing the liquid contained in the metered reaction volume 32 in the sample channel 30.
  • the first hydrophobic stop 61 separates the sample channel 30 from the expelling channel 40 so as to prevent liquid from entering the expelling channel 40.
  • the second section 32 of the sample channel 30 and the expelling channel 40 are aligned, whereas the first section 31 of the sample channel 30 extends from the second section 32 in an angle.
  • the first hydrophobic stop 61 is placed to connect the expelling channel 40 to the sample channel 30 at the junction of the first and second sections 31, 32 of the sample channel 30.
  • the first hydrophobic stop 61 is placed to allow capillary flow between the first and second section 31, 32 of the sample channel 30 but to prevent capillary flow between the sample channel 30 and the expelling channel 40.
  • a pneumatic source 80 Connected to the expelling channel 40 is a pneumatic source 80.
  • the pneumatic source 80 is connected to the end of the expelling channel 40 opposing the first hydrophobic stop 61.
  • the pneumatic source 80 may simply be a blister pump or similar manual device for increasing the pressure inside the expelling channel 40.
  • the blister pump may be constructed by providing the top substrate 210 with a through hole connecting the expelling channel 40 to the ambient space.
  • the top part of the through hole may be provided with a supple membrane which acts as a diaphragm or blister pump.
  • the membrane may extend over the opening in the top substrate 210 so as to increase the volume defined by the membrane.
  • the volume defined by the membrane is dimensioned to be enough to increase the pressure inside the expelling channel 40 to urge liquid contained in the metered sample volume 32 past the second hydrophobic stop 62.
  • the pneumatic source 80 may be simple port for introducing pressurised air into the inner flow channel. Accordingly, the pneumatic source 80 may take the shape of a pneumatic connector for coupling thereon a compressor tube, bellows, or similar.
  • a waste channel 20 Connected also to the inlet 10 is a waste channel 20 which is formed into the body 200.
  • the waste channel 20 leads from the inlet towards a waste reservoir 52 which is constructed to receive and hold liquid.
  • the waste reservoir 52 preferably includes an absorbent material, a capillary pump or another means of attracting liquid entering into the inner flow volume through the inlet 10.
  • the waste reservoir 52 is designed to receive and hold a substantial volume of fluid.
  • the waste reservoir 52 may include absorption material 70 or a capillary pump to further attract the liquid.
  • the waste reservoir 52 is in fluidic connection to the ambient space through an air outlet 11 for exhausting air trapped in the inner flow volume, when liquid is being pushed along the channel 30.
  • the air outlet 11 may be a simple hole or a valved passage provided to the top substrate 210 or bottom substrate 230 or both.
  • the sample liquid is administered into the inlet 10 by a pipette or by pouring from a vessel.
  • a funnel of some sort for domestic use it may be advantageous to use a funnel of some sort to improve accuracy.
  • the mass of the sample liquid accumulated into the volume of the inlet 10 combined with the appropriately selected dimensions for the inner flow channel urges the sample liquid onward in the inner flow channel.
  • the inner flow channel is preferably two-dimensional, whereby the liquid flow need not exceed resistance caused by elevations.
  • a device featuring only a two-dimensional inner flow channel may be produced by a roll-to-roll manufacturing method which is very beneficial for mass production.
  • a stream of liquid flow proceeds down the sample channel 30.
  • the sample liquid first travels across the first section 31 of the sample channel 30, wherein the first hydrophobic stop 61 prevents the liquid from entering the expelling channel 40.
  • the liquid proceeds across the second section 32 of the sample channel 30 until it is stopped by the second hydrophobic stop 62.
  • a stream of liquid flow proceeds up the waste channel 20 spurred by capillary action and potentially the absorbent material housed in the waste reservoir 52.
  • the absorbent material has the added benefit that the liquid is not returned to the channel.
  • the absorbent material also limits the speed in which the liquid is moved in the inner flow channel. This yields the benefit of controlling the reaction time.
  • the sample channel 30 is filled with the sample liquid, the inlet 10 is empty or substantially empty, the waste channel 20 is filled and the waste reservoir 52 is at least partly filled.
  • the inlet 10 is sealed by applying tape, inserting a cork or otherwise. The sealing of the inlet 10 is preferably air tight. With the inlet 10 sealed the sample liquid in the metered sample volume 32 is expelled into the sample reservoir 51.
  • the pneumatic source 80 is operated to pressurize the expelling channel 40. In case a blister pump is employed, a simple depression of the membrane is enough to create the impulse needed to start the liquid flow in the inner flow channel.
  • the elevated pressure in the expelling channel 40 is transmitted to the sample channel 30, whereby the liquid therein is pressurized as well so as to exceed the flow threshold of the second hydrophobic stop 62. It is to be noted that the hydrophobic stops do not arrest air flow to a considerable degree. Once the flow threshold of the second hydrophobic stop 62 has been exceeded, the liquid in the metered sample volume 32 will flow into the sample reservoir 51 potentially encouraged by the therein contained absorption material 70 or capillary pump. The liquid contained in the first section 31 of the sample channel 30 may proceed into the waste reservoir 52 through the closed inlet 10 and the waste channel 20 or be drawn into the sample reservoir 51 depending on the flow resistance created by the inlet 10. If the seal closes the communication between the sample channel 30 and the waste channel 20, the latter option will apply.
  • the above process will have resulted in the sample to have been flowed past the detection zone 33 in the reaction volume 32, wherein the sample interacted with the capture antibodies.
  • the microfluidic chip 100 With the metered reaction volume 32 emptied, the microfluidic chip 100 is ready for optical analysis for the residual sample portion remaining in the detection zone 33.
  • the optical analysis, particularly immune / sandwich assay may be, for example, a fluorescence or colorimetric test which analyses residual substances in the metered sample volume 32.

Abstract

Une nouvelle puce microfluidique est proposée pour effectuer un test chimique ou biochimique dans un volume de réaction dosé (32). La puce microfluidique (100) a un corps (200) qui définit un volume d'écoulement interne. Une entrée (10) a été fournie au corps (200) pour relier le volume d'écoulement interne à l'espace ambiant. Un canal de déchets (20) fait partie du volume d'écoulement interne et est en communication fluidique avec l'entrée (10). Un canal d'échantillon (30) fait également partie du volume d'écoulement interne et est en communication fluidique avec l'entrée (10). Le canal d'échantillon (30) comprend une première butée hydrophobe (61) et une seconde butée hydrophobe (62) à une certaine distance de la première butée hydrophobe (61) de façon à fournir un volume de réaction dosé (32) entre celles-ci. Un canal d'expulsion (40) est en communication fluidique avec le volume de réaction dosé (32) du canal d'échantillon (30) à travers la première butée hydrophobe (61). Un réservoir d'échantillon (51) est en communication fluidique avec le volume de réaction dosé (32) du canal d'échantillon (30) à travers la seconde butée hydrophobe (62).
PCT/FI2018/050492 2017-06-30 2018-06-25 Puce microfluidique et procédé de production d'une puce microfluidique WO2019002678A1 (fr)

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US16/627,373 US11759782B2 (en) 2017-06-30 2018-06-25 Microfluidic chip and a method for the manufacture of a microfluidic chip
EP18823238.3A EP3645165A4 (fr) 2017-06-30 2018-06-25 Puce microfluidique et procédé de production d'une puce microfluidique
CN201880044196.0A CN110891686B (zh) 2017-06-30 2018-06-25 微流控芯片和制造微流控芯片的方法

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FI20175637A FI128087B (en) 2017-06-30 2017-06-30 Microfluidic chip and a method of making a microfluidic chip

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022005146A1 (fr) * 2020-06-29 2022-01-06 성균관대학교산학협력단 Appareil de diagnostic moléculaire utilisant une résonance plasmonique de surface à base de graphène métallique, fabriqué par un processus rouleau à rouleau, et son procédé de fabrication

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114505106B (zh) * 2022-01-29 2023-02-03 南京岚煜生物科技有限公司 优化磁性混匀效果的主动微流控芯片及其使用方法
CN115016263A (zh) * 2022-05-27 2022-09-06 福州大学 连续微流控生物芯片下基于drl的控制逻辑设计方法

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999019717A1 (fr) * 1997-10-15 1999-04-22 Aclara Biosciences, Inc. Dispositif a microstructure stratifiee et procede de fabrication de ce dispositif
US6911183B1 (en) * 1995-09-15 2005-06-28 The Regents Of The University Of Michigan Moving microdroplets
US20100143194A1 (en) * 2008-12-08 2010-06-10 Electronics And Telecommunications Research Institute Microfluidic device
US20110008210A1 (en) * 2008-02-21 2011-01-13 Valtion Teknillinen Tutkimuskeskus Biosensor and a related manufacturing method
WO2011108333A1 (fr) * 2010-03-05 2011-09-09 コニカミノルタオプト株式会社 Procédé de fabrication d'une puce de détection microfluidique
US20120196280A1 (en) * 2009-07-17 2012-08-02 Norchip A/S Microfabricated device for metering an analyte
US20150024477A1 (en) * 2012-05-16 2015-01-22 Panasonic Healthcare Co., Ltd. Biosensor chip, and biosensor device equipped with same
EP2658653B1 (fr) * 2010-12-30 2015-03-04 Abbott Point Of Care, Inc. Cartouche de bioanalyse avec partie pour la manipulation d'échantillons et chambre d'analyse
WO2016069091A1 (fr) * 2014-08-15 2016-05-06 California Institute Of Technology Couvercle de pompage : dispositifs et procédés pour la génération programmable de pression positive et de pression négative
EP2363207B1 (fr) * 2001-03-28 2016-10-05 Handylab, Inc. Procédés pour commander des dispositifs microfluidiques digitals

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0293519A1 (fr) 1987-06-03 1988-12-07 James F. Brown Dispositif de commande d'écoulement dans des capillaires
US4859421A (en) 1987-06-23 1989-08-22 The Research Foundation Of State University Of New York Disposable antigen concentrator and detector
DE10302721A1 (de) 2003-01-23 2004-08-05 Steag Microparts Gmbh Mikrofluidische Anordnung zum Dosieren von Flüssigkeiten
EP2011630A1 (fr) 2007-07-03 2009-01-07 F. Hoffmann-La Roche AG Procédé destiné à la réalisation d'un élément d'analyse
GB201014805D0 (en) * 2010-09-07 2010-10-20 Multi Sense Technologies Ltd Microfluidics based assay device
EP2665957B1 (fr) 2011-01-21 2015-03-11 Fluimedix APS Procédé de régulation d'un écoulement
EP3663408B1 (fr) 2011-10-11 2024-05-01 QIAGEN GmbH Procédé de traitement d'échantillons et cartouche de traitement d'échantillons
WO2015017591A1 (fr) 2013-07-30 2015-02-05 Express Diagnostics Int'l., Inc. Dispositifs d'écoulement latéral et leurs procédés de fabrication et d'utilisation
US20150093838A1 (en) 2013-10-01 2015-04-02 James P. Landers Microfluidic valve systems
US9283560B2 (en) 2013-11-22 2016-03-15 Sharp Kabushiki Kaisha Passive microfluidic metering device

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6911183B1 (en) * 1995-09-15 2005-06-28 The Regents Of The University Of Michigan Moving microdroplets
WO1999019717A1 (fr) * 1997-10-15 1999-04-22 Aclara Biosciences, Inc. Dispositif a microstructure stratifiee et procede de fabrication de ce dispositif
EP2363207B1 (fr) * 2001-03-28 2016-10-05 Handylab, Inc. Procédés pour commander des dispositifs microfluidiques digitals
US20110008210A1 (en) * 2008-02-21 2011-01-13 Valtion Teknillinen Tutkimuskeskus Biosensor and a related manufacturing method
US20100143194A1 (en) * 2008-12-08 2010-06-10 Electronics And Telecommunications Research Institute Microfluidic device
US20120196280A1 (en) * 2009-07-17 2012-08-02 Norchip A/S Microfabricated device for metering an analyte
WO2011108333A1 (fr) * 2010-03-05 2011-09-09 コニカミノルタオプト株式会社 Procédé de fabrication d'une puce de détection microfluidique
EP2658653B1 (fr) * 2010-12-30 2015-03-04 Abbott Point Of Care, Inc. Cartouche de bioanalyse avec partie pour la manipulation d'échantillons et chambre d'analyse
US20150024477A1 (en) * 2012-05-16 2015-01-22 Panasonic Healthcare Co., Ltd. Biosensor chip, and biosensor device equipped with same
WO2016069091A1 (fr) * 2014-08-15 2016-05-06 California Institute Of Technology Couvercle de pompage : dispositifs et procédés pour la génération programmable de pression positive et de pression négative

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
FEYSSA, B. ET AL.: "Patterned Immobilization of Antibodies within Roll- to-Roll Hot Embossed Polymeric Microfluidic Channels", PLOS ONE, vol. 8, no. 7, 18 July 2013 (2013-07-18), pages 1 - 11, XP055569186, Retrieved from the Internet <URL:https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0068918> [retrieved on 20180905] *
HAKALAHTI, L. ET AL.: "Your lab on a chip - Roll-to-roll hot- embossed microfluidics for life sciences applications", FREEDOM OF DESIGN. RESEARCH, DEVELOPMENT AND COMMERCIALISATION HIGHLIGHTS IN PRINTED INTELLIGENCE 2011 - 2012, 2012, pages 32 - 34, XP055569190, Retrieved from the Internet <URL:https://www.vtt.fi/files/services/ele/printed_intelligence_2012_2.pdf> [retrieved on 20180907] *
IWAI, K. ET AL.: "Finger-powered microfluidic systems using multilayer soft lithography and injection molding processes", LAB ON A CHIP, vol. 14, no. 19, 2014, pages 3790 - 3799, XP055569195 *
KANG, T. H. ET AL.: "Portable multi-immunosensing lab-on-a-chip (LOC) triggered by air bladder", BIOMEMS AND NANOTECHNOLOGY III CONFERENCE, 5 December 2007 (2007-12-05), Canberra , Australia, XP055569192 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022005146A1 (fr) * 2020-06-29 2022-01-06 성균관대학교산학협력단 Appareil de diagnostic moléculaire utilisant une résonance plasmonique de surface à base de graphène métallique, fabriqué par un processus rouleau à rouleau, et son procédé de fabrication

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US20210146357A1 (en) 2021-05-20
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FI20175637A1 (en) 2018-12-31
CN110891686A (zh) 2020-03-17
US11759782B2 (en) 2023-09-19
EP3645165A4 (fr) 2021-03-17
FI128087B (en) 2019-09-13
EP3645165A1 (fr) 2020-05-06

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